Adenovirus vector-mediated perforin expression driven by a glucocorticoid-inducible promoter inhibits tumor growth in vivo

Narumi Ko, Akira Kojima, Ronald Crystal

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

To evaluate the concept that in vivo transfer of perforin complementary DNA (cDNA) will suppress tumor growth, we constructed an adenovirus vector (AdGRE.PFP) carrying perforin cDNA driven by the glucocorticoid response element (GRE) promoter. We infected A549 lung carcinoma cells with this vector in vitro and in vivo, and evaluated cell growth over time. In the presence of dexamethasone, in vitro infection of A549 cells with the AdGRE.PFP vector yielded perforin messenger RNA (mRNA) transcripts and effectively suppressed A549 cell growth. In accord with these in vitro observations, administration of dexamethasone following direct injection of AdGRE.PFP into established subcutaneous A549 tumors in nude mice resulted in a marked reduction in tumor growth as compared with AdGRE.PFP infection without dexamethasone or with dexamethasone alone. These observations suggest that regulable, adenovirus-mediated gene expression of perforin cDNA may have potential as a strategy for local control of tumor cell growth.

Original languageEnglish
Pages (from-to)936-941
Number of pages6
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume19
Issue number6
Publication statusPublished - 1 Dec 1998
Externally publishedYes

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Perforin
Adenoviridae
Carcinogens
Dexamethasone
Glucocorticoids
Tumors
Cell growth
Complementary DNA
Growth
Neoplasms
Direct injection
Response Elements
Gene expression
Infection
Nude Mice
Cells
Messenger RNA
Carcinoma
Gene Expression
Lung

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

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abstract = "To evaluate the concept that in vivo transfer of perforin complementary DNA (cDNA) will suppress tumor growth, we constructed an adenovirus vector (AdGRE.PFP) carrying perforin cDNA driven by the glucocorticoid response element (GRE) promoter. We infected A549 lung carcinoma cells with this vector in vitro and in vivo, and evaluated cell growth over time. In the presence of dexamethasone, in vitro infection of A549 cells with the AdGRE.PFP vector yielded perforin messenger RNA (mRNA) transcripts and effectively suppressed A549 cell growth. In accord with these in vitro observations, administration of dexamethasone following direct injection of AdGRE.PFP into established subcutaneous A549 tumors in nude mice resulted in a marked reduction in tumor growth as compared with AdGRE.PFP infection without dexamethasone or with dexamethasone alone. These observations suggest that regulable, adenovirus-mediated gene expression of perforin cDNA may have potential as a strategy for local control of tumor cell growth.",
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